Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580695 | SCV000681828 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 2276 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV000822493 | SCV000963300 | uncertain significance | Familial adenomatous polyposis 1 | 2018-08-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 2276 of the APC protein (p.Pro2276Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 489486). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Sema4, |
RCV000580695 | SCV002534541 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-12 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV000580695 | SCV002664740 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-27 | criteria provided, single submitter | clinical testing | The p.P2276S variant (also known as c.6826C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 6826. The proline at codon 2276 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |